Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine

Muhammad Yaqoob, Charles L. Edelstein, Eric Wieder, Ahmed M. Alkhunaizi, Patricia E. Gengaro, Raphael A. Nemenoff, Robert W. Schrier

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Abstract

In the present study, we directly monitored nitric oxide (NO) with an amperometric NO-sensor in suspensions of rat proximal tubules. Hypoxia-stimulated NO generation was characterized by an initial rise and a subsequent sustained increase which preceded cell membrane damage as assessed by lactic dehydrogenase (LDH) release. In contrast, the NO concentration remained unmeasurable in normoxic controls. Nitro-L-arginine-methyl ester (L-NAME) prevented the hypoxia-induced increase in NO in a dose dependent manner in parallel with incremental cytoprotection. The hypoxia-induced elevation in NO and the associated membrane injury were both markedly prevented by extracellular acidosis (pH 6.95). In vitro proximal tubular nitric oxide synthase (NOS) activity (3H-arginine to 3H-citrulline assay) was pH-dependent with optimum activity at pH 8.0 and greatly reduced activity at acidic pH even in the presence of calcium and co-factors. However, glycine, a well recognized cytoprotective agent, did not attenuate the NO concentration during hypoxia. The present study therefore provides direct evidence that NO is generated by rat proximal tubules during hypoxia and demonstrates that the protective effect of low pH against hypoxic rat tubular injury is associated with an inhibition of this NO production.

Original languageEnglish (US)
Pages (from-to)1314-1319
Number of pages6
JournalKidney International
Volume49
Issue number5
StatePublished - 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

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Yaqoob, M., Edelstein, C. L., Wieder, E., Alkhunaizi, A. M., Gengaro, P. E., Nemenoff, R. A., & Schrier, R. W. (1996). Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine. Kidney International, 49(5), 1314-1319.